Effectiveness and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a systematic review and meta-analysis

Abstract

Background: Studies in recent years have shown that PD-1/PD-L1 inhibitors may have better effectiveness in patients with advanced or recurrent endometrial cancer. The effectiveness of PD-1/PD-L1 inhibitors is thought to be related to mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) classification in advanced or recurrent endometrial cancer. This study aims to evaluate the effectiveness of PD-1/PD-L1 inhibitors in patients classified as dMMR and pMMR.Methods: Medical databases were searched to identify relevant publications up to 30 November 2022. The primary outcome was comparison of objective response rate (ORR) in patients with dMMR and pMMR following treatment with PD-1/PD-L1 inhibitors; secondary outcomes were single-group ORR in patients with dMMR and in patients with pMMR, respectively.Results: Eleven studies were eligible for analysis and patients with advanced or recurrent endometrial cancer with molecular classification of dMMR had a higher total ORR than those with pMMR [odds ratio (OR), 7.70; 95% confidence interval (CI), 3.22–18.38; p < 0.01], with low evidence of between-study heterogeneity (I2 = 0%). The total ORR of patients with advanced or recurrent endometrial cancer with molecular type dMMR was 51.9% (95% CI, 33.6%–69.9%). The overall ORR of patients with advanced or recurrent endometrial cancer with molecular type pMMR was 16.1% (95% CI, 5.5%–30.3%).Conclusion: In our including studies, the patients with advanced or recurrent endometrial cancer with molecular types of dMMR and pMMR, following treatment with PD-1/PD-L1 inhibitors, the total ORR of patients with dMMR was higher than that of patients with pMMR. Since the current number of studies is not very large, it is possible that more studies will be published in the future and more precise results will be discussed further.

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis

“…The incidence of abnormal (ectopic) cells in endometriosis-affected endometrium is significantly elevated compared to normal endometrial tissue. While prior studies have not indicated a heightened risk of malignant transformation in endometriosis patients, they have identified an increased incidence of ovarian cancer, endometrial cancer, non-Hodgkin’s lymphoma, colorectal cancer, thyroid cancer, and melanoma within this population [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

“…Elucidating the role of the PD-1/PD-L1 pathway in endometriosis opens new avenues for targeted therapeutic interventions. Inhibitors of PD-1 and PD-L1, which are currently utilized in oncology, hold the potential for modulating the immune response in endometriosis [ 31 , 32 ]. Therapeutic strategies aimed at downregulating PD-L1 expression or blocking the PD-1/PD-L1 interaction could enhance the immune system’s efficacy against ectopic endometrial tissue, thereby introducing novel treatment options for endometriosis management.…”